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NMSP Exam 2 > Lecture 1: Pharmacology of Neurological Infections > Flashcards

Lecture 1: Pharmacology of Neurological Infections Flashcards

1
Q

What is the standard emperic antibiotic regimen for acute pyogenic meningitis?

A
  • [Cefotaxime or ceftriaxone] + vancomycin
  • Ampicillin added in older patients (>50 years)
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2
Q

What’s the standard treatment for infantile meningitis caused by H. influenzae type B?

A
  • Hib vaccine
  • Cefotaxime or ceftriaxone
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3
Q

What’s the empiric treatment for acute pyogenic meningitis in patients with a beta-lactam allergy?

Beta-lactam allergy in patients age >50?

A
  • Standard = Vancomycin + moxifloxacin
  • >50 y/o = Vancomycin + moxifloxacin + TMP/SMX
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4
Q

What’s the empiric treatment for acute pyogenic meningitis in immunocompromised patients?

A

Vancomycin + ampicillin + [cefepime or meropenem]

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5
Q

Which virus family and viruses in this family are the major cause of acute aseptic meningitis?

A
  • Enteroviruses
  • Coxsackievirus, echovirus
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6
Q

CSF findings (immune cells, protein, glucose, and opening pressure) seen with acute aseptic meningitis?

A
  • Lymphocytic pleocytosis
  • Moderate protein elevation
  • Normal glucose
  • Opening pressure can be normal or elevated
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7
Q

What is the standard of care if you begin antibiotics after a lumbar puncture for suspected meningits, but the bacterial cultures are negative?

A

Discontinue antibiotics

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8
Q

What are the two 3rd gen. Cephalosporins used for meningitis?

A
  • Cefotaxime
  • Ceftriaxone
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9
Q

What is the 4th gen. Cephalosporin used in the treatment of meningitis?

A

Cefepime

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10
Q

What is the Glycopeptide used in the treatment of meningitis/brain abscesses/subdural empyema?

A

Vancomycin

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11
Q

What is the Carbapenem used in the treatment of meningitis/brain abscesses/subdural empyema?

A

Meropenem

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12
Q

What is the Aminopenicillin used in the treatment of meningitis?

A

Ampicillin

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13
Q

What is the Fluoroquinolone used in the treatment of meningitis?

A

Moxifloxacin

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14
Q

What are the Benzylpyrimidine/Sulfonamide used in the treatment of meningitis?

A

Trimethoprim/Sulfamethoxazole (TMP/SMX)

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15
Q

What is the CSF content (immune cells, glucose, and protein) seen with a brain abscess?

A
  • High white cell count
  • Increased protein concentration
  • Normal glucose content
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16
Q

What are the most common pathogens that cause brain abscesses?

A
  • Viridans streptococci
  • S. aureus
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17
Q

Which group of pathogens is the most likely culprit for a brain abscess in an immunocompetent vs. immunocompromised patient?

A
  • Immunocompetent = bacteria
  • Immunocompromised = fungi (can be bacterial too)
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18
Q

What is the standard of care for a brain abscess?

A
  • Surgery + antibiotic reduces otherwise high mortality rate to 10%
  • Aspiration
  • Craniotomy to drain abscess or to totally remove it
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19
Q

What is the empiric therapy of brain abscess with unknown source?

A

Vancomycin + [ceftriaxone or cefotaxime] + metronidazole

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20
Q

Which antibiotic is used to cover aerobic and anaerobic streptococci (mouth flora) involved in a brain abscess?

A

Penicillin G

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21
Q

Which antibiotic can readily penetrate a brain abscess and is often combined with other agents during treatment of brain abscesses?

A

Metronidazole

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22
Q

Which antibiotic can be used as a substitue for Penicillin G while treating a brain abscess?

A

Ceftriaxone or Cefotaxime

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23
Q

Which organisms are covered by Ceftriaxone and Cefotaxime?

A
  • Most aerobic and microaerophilic streptococci
  • Many enterobacteriaceae
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24
Q

Which antibiotics are used if a brain abscess complicates a neurosurgical procedure or cases in which the abscess culture grows P. aeruginosa?

A

Ceftazidime, cefepime, or meropenem

25
What is the standard for the use of Vancomycin in the treatment of brain abscesses? When would you stop using? Which antibiotics will be substituted for the Vancomycin?
- Included in tx regimen **until** culture and susceptibility results are available - **No MRSA** = **NO** vancomycin - **Naficillin** or **oxacillin** should be **substituted** for vancomycin
26
What are the three Cephalosporin: 3rd gen. used in the treatment of brain abscesses/subdural empyema?
- Cefotaxime - Ceftriaxone - Ceftazidime
27
What's a Subdural empyema?
Produced by bacteria (and rarely fungal) **infections of the skull bones or air sinuses** that spread to the **subdural space**
28
What are the common pathogens that cause subdural empyemas? Following neurosurgical procedures or head trauma?
- **Aerobic** and **anaerobic** **S****treptococci**,**S****taphylococci**, **E****nterobacteriaceae**, and**anaerobic bacteria** - **Following neuro procedure/trauma**: Staphylococci (**MRSA**) and gram-negative bacilli (***P. aeruginosa)***
29
What is the immediate treatment for a subdural empyema?
- **Medical emergency!** - Surgery to evacuate the empyema - Antibiotic therapy
30
What is the empiric antibiotic therapy for subdural empyema that is **community acquired?**
[Cefotaxime or ceftriaxone] + vancomycin + metronidazole
31
What is the empiric antibiotic therapy for subdural empyema that is **hospital acquired (*P. aeruginosa* or MRSA)?**
Meropenem + vancomycin
32
What are 4 types of Viral Meningoencephalitis?
1) Parenchymal infection of the brain: associated w/ meningoencephalitis and encephalomyelitis 2) Arthropod borne viral encephalitis 3) Subacute sclerosis panencephalitis (SSPE): measles 4) Poliomyelitis
33
SSPE caused by measles is characterized by?
- Variable inflammation of white and grey matter - Neurofibrillary tangles
34
What are the initial signs of Poliomyelitis?
Mild gastroenteritis
35
Which immunoglobulins are produced with a live vaccine? Killed vaccine?
Live = IgA and IgG Killed = IgG
36
Is there cell-mediated immunity produced with a live vaccine and killed vaccine?
- **Live vaccine** = yes - **Killed vaccine** = weakly or none
37
What type of vaccine is the MMR?
Live attenuated
38
What are the 2 types of poliomyelitis vaccine and which is safer?
1) **Inactivated poliovirus vaccine (IPV)**: **killed virus** vaccine; does **NOT** cause vaccine-associated paralytic poliomyelitis 2) **Live attenuated oral poliovirus vaccine (OPC)**: **can** cause polio in a small % of pts
39
Which fungi is a common cause of fungal meningoencephalitis? Who is particularly at risk? CSF finding?
- *Cryptococcal meningitis* - Common opportunistic infection in setting of AIDS - CSF contents = likely high protein concentration
40
How does fungal meningoencephalitis manifest; appearance of brain sections?
- Manifests as **chronic meningitis** affecting the **basal leptomeninges** - Appears of "**soap bubbles**" on whole-brain sections
41
What is the common clinical presentation for Fungal meningoencephalitis?
- Stiff neck, photophobia, and vomiting - Lethargy and confusion
42
Which infection should you hav a high suspicion of with advanced HIV patients that have a CD4 count \<100 cells/uL and presenting with stiff neck, photophobia, and vomiting?
*Cryptococcal meningitis*
43
Which antibiotics are used for the **induction phase** and then **consolidation phase** of therapy for funal meningoencephalitis?
- **Induction phase**: Amphotericin B + Flucytosine (5-FC) - **Consolidation:** Fluconazole
44
What is Ergosterol?
- Vital part of cell membranes of fungi (not found in human cell membranes) - Most anti-fungal agents bind ergosterol w/ a higher affinity than cholesterol
45
What is the MOA of the anti-fungal, Amphotericin B?
- Forms complex w/ ergosterol and disrupts the fungal cell membrane - Leads to cytoplasmic leakage and fungal cell death
46
How is the anti-fungal, Amphotericin B administered? Adverse effects?
- Given IV and **directly** into the CSF (not absorbed orally) - _Adverse effects:_ - Renal toxicity - **Acute febrile rxn**: chills and fever, common - Anemia \*Often nicknamed in the clinic: **AWFUL-tericin or Ampho-TERRIBLE**
47
What is the MOA of the anti-fungal, Flucytosine (5-FC)? Why should it not be used alone?
- Antimetabolite - Converted to **5-fluorouracil (5-FU)** inside fungal cells - **Inhibits** DNA and RNA synthesis (similar structure to **uracil** so can integrate itself into DNA and RNA causing **cell death** - **Rapid resistance** develops if used alone
48
What are the possible adverse effects of the anti-fungal, Flucytosine (5-FC)?
- Conversion of 5-FC to 5-FU **OUTSIDE** of the fungal cells - Bone marrow depression, nausea, vomiting, and diarrhea \*Logically, will affect the rapidly proliferating cells of your body, like within the bone marrow and GI mucosa!!!
49
What is the MOA of the anti-fungals, Fluconazole, Azole, and Triazole? How easy do they get into CSF?
- **Inhibit** ergosterol synthesis by **inhibiting** fungal P450 enzymes - Very good CSF penetration
50
What are the adverse effects of Fluconazole?
Limited, widest therapeutic index of all the azoles
51
Which 4 antibiotic classes + one drug not belonging to a class should **NOT** be used to treat neuroinfections?
1) Cephalosporins: 1st gen --\> **Cefazolin** 2) Aminoglycosides: (-**mysin** and **-micin**) 3) Tetracyclines: (-**cyclines**) 4) **Macro**lides: (-**mysin** and **-micin**) 5) No class: Clinda**mycin**
52
How is Metronidazole activated?
- Anaerobic pathogens contain an electron transport system w/ a **high negative redox potential**, which **donates electrons to Metronidazole** - When electron is donated, a highly reactive **nitro radical anion** is formed; allows for the killing of organisms by means of **radical-mediated DNA damage**
53
What is one major way of resisting Metronidazole?
- Increasing intracellular levels of O2 - Resistance correlates w/ **impaired O2 scavenging**, which leads to increased intracellular O2 levels
54
Metronidazole is active against which pathogens?
- Flagellated protozoa: *T. vaginalis* and *G. lamblia* - *E. histolytica* (protozoan) - Anaerobic cocci and Anaerobic gram-negative bacilli - *Helicobacter* and *Campylobacter spp.* (gram-negative) - *Clostridium spp.* (gram-positive bacilli)
55
What are adverse effects that are unique to Metronidazole?
- **Metallic taste** in pt's mouth - **Disulfiram-like effect:** induces vomiting if alcohol consumed during or within 3 days of treatment; also flushing, abdominal discomfort, or headache
56
CSF content associated with acute pyogenic meningits?
- Increased **neutrophils** - Increased protein - Decreased glucose
57
Which class does Metronidazole belong to?
5-nitroimidazoles
58
What are the concerns with the use of live vaccines?
- Attenuated viral mutants **revert to virulence** either during vaccine production or in the immunized person: **Polio, not measles** and is **pathogenic** in **immunocompromised** pts - **Excretion of live virus** to infect other: **Herd immunity** and **Double edged sword**

NMSP Exam 2 (15 decks)

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